RRC ID 59631
Author Zaarur N, Desevin K, Mackenzie J, Lord A, Grishok A, Kandror KV.
Title ATGL-1 mediates the effect of dietary restriction and the insulin/IGF-1 signaling pathway on longevity in C. elegans.
Journal Mol Metab
Abstract OBJECTIVE:Animal lifespan is controlled through genetic pathways that are conserved from nematodes to humans. Lifespan-promoting conditions in nematodes include fasting and a reduction of insulin/IGF signaling. Here we aimed to investigate the input of the Caenorhabditis elegans homologue of the mammalian rate-limiting lipolytic enzyme Adipose Triglyceride Lipase, ATGL-1, in longevity control.
METHODS:We used a combination of genetic and biochemical approaches to determine the role of ATGL-1 in accumulation of triglycerides and regulation of longevity.
RESULTS:We found that expression of ATGL is increased in the insulin receptor homologue mutant daf-2 in a FoxO/DAF-16-dependent manner. ATGL-1 is also up-regulated by fasting and in the eat-2 loss-of-function mutant strain. Overexpression of ATGL-1 increases basal and maximal oxygen consumption rate and extends lifespan in C. elegans. Reduction of ATGL-1 function suppresses longevity of the long-lived mutants eat-2 and daf-2.
CONCLUSION:Our results demonstrate that ATGL is required for extended lifespan downstream of both dietary restriction and reduced insulin/IGF signaling.
Volume 27
Pages 75-82
Published 2019-9-1
DOI 10.1016/j.molmet.2019.07.001
PII S2212-8778(19)30482-X
PMID 31311719
PMC PMC6717769
MeSH Animals Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / metabolism* Fasting Insulin / metabolism* Insulin-Like Growth Factor I / metabolism* Lipase / metabolism* Longevity Signal Transduction*
IF 6.448
Times Cited 1
C.elegans tm3116